Gene Therapy Technique Cures Cystic Fibrosis in Culture Model

CF is a genetic disease, and the mutant protein is a chloride ion channel (CFTR) that normally regulates ion and fluid transport on the airway surface.

Investigators at the University of North Carolina (Chapel Hill, USA) reasoned that the most appropriate means for delivering a gene to lung tissue was a virus that specialized in invading the lungs. They created an in vitro model of CF by growing cultures of ciliated surface airway epithelium (CF HAE) cells obtained from a CF patient. The cultures were then treated with parainfluenza virus that had been genetically engineered to carry the normal CFTR gene.

Results published in the July 21, 2009, online edition of the journal PLoS Biology revealed that the vector delivered CFTR to more than 60% of airway surface epithelial cells, and the expression of CFTR protein in the CF HAE cells was approximately 100-fold higher than endogenous levels found in normal HAE cells.

By titering the amount of CFTR gene in the vector, the investigators were able to determine that uptake of the gene by 25% of the cells was sufficient to restore normal function to the entire culture.

"We discovered that if you take a virus that has evolved to infect the human airways, and you engineer a normal CFTR gene into it, you can use this virus to correct all of the hallmark CF features in the model system that we used,” said senior author Dr. Raymond J. Pickles, associate professor of microbiology and immunology at the University of North Carolina. "This is the first demonstration in which we have been able to execute delivery in an efficient manner. When you consider that in past gene therapy studies, the targeting efficiency has been somewhere around 0.1% of cells, you can see this is a giant leap forward.”

"We have not generated a vector that we can go out and give to patients now,” said Dr. Pickles, "but these studies continue to convince us that a gene replacement therapy for CF patients will some day be available in the future.”

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